NAD+ Studies

This page is an addendum to our NAD+ Blog Post.

SEE THE POST HERE (< you can also find where we purchase it from at that page)

Overall Health Benefits of NAD+

NAD+ benefits include boosting cellular energy production, enhancing DNA repair, and promoting healthy aging by supporting metabolic functions and reducing oxidative stress. Additionally, NAD+ plays a crucial role in maintaining mitochondrial function and improving cognitive health.

Numbers correspond to references below:

Extends lifespan [1-15]
Produces anti-aging benefits [16-24]
Increases energy levels [25-33]
Promotes weight loss [34-48]
Increases muscle mass and strength [19, 22, 49-55]
Improves cognitive function [11, 56-96]
Fights cancer [97-104] (not affirming simply sharing research)
Improves cardiovascular health [2, 105-127]
Lowers blood pressure [128-131]
Improves blood sugar levels [132-134]
Boosts immune function [49, 135-146]
Improves liver health [147-155]
Improves kidney health [156-165]

Key Takeaways

Energy Production: NAD+ is essential for cellular energy production, supporting the conversion of nutrients into usable energy.
DNA Repair: It plays a crucial role in DNA repair mechanisms, helping to maintain genetic integrity and reduce the risk of mutations.
Healthy Aging: NAD+ levels decline with age, and supplementing it can promote healthy aging by improving metabolic functions and reducing oxidative stress.
Mitochondrial Function: It supports mitochondrial health, ensuring efficient energy production and reducing cellular damage.
Cognitive Health: NAD+ has been linked to improved cognitive function and protection against neurodegenerative diseases like Alzheimer’s and Parkinson’s.

What is Nicotinamide Adenine Dinucleotide?

Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme that is present in each living cell in the body.

It is produced from the breakdown of nicotinamide riboside (niagen), an alternative form of vitamin B3 (niacin). NAD+ plays an integral role in energy production and regulation of vital cellular processes such as DNA repair, strengthening cells’ defense systems, conversion of food into a usable form of energy, and regulation of circadian rhythm.

How NAD+ Works

NAD+ converts nutrients into adenosine triphosphate, a compound that provides energy to living cells. Aside from this important function, it works together with various forms of proteins to carry out a wide array of biological processes such as DNA repair, calcium signaling, maintenance of cell energy and chromosomal integrity, and gene expression.

From Genemedics

Related Research for NAD+

References

Monaghan, P., & Haussmann, M. F. (2006). Do telomere dynamics link lifestyle and lifespan?. Trends in ecology & evolution, 21(1), 47–53. https://doi.org/10.1016/j.tree.2005.11.007. View Summary –Do telomere dynamics link lifestyle and lifespan?In their paper, Monaghan and Haussmann (2006) investigate the potential link between lifestyle factors and telomere dynamics, which are key determinants of cellular aging and lifespan. Telomeres, the protective caps at the ends of chromosomes, undergo shortening with each cell division, eventually leading to cellular senescence and aging. The authors explore how lifestyle choices, such as diet, exercise, and stress levels, may influence telomere length and maintenance mechanisms.Their review highlights emerging evidence suggesting that certain lifestyle factors, such as regular exercise and a healthy diet, may promote telomere length maintenance and delay cellular aging. Conversely, factors like chronic stress and unhealthy behaviors may accelerate telomere shortening and contribute to premature aging.Full article on https://www.cell.com/trends/ecology-evolution/fulltext/S0169-5347(05)00371-X?large_figure=true
Monaghan P. (2010). Telomeres and life histories: the long and the short of it. Annals of the New York Academy of Sciences, 1206, 130–142. https://doi.org/10.1111/j.1749-6632.2010.05705.x. View Summary –Telomeres and life histories: the long and the short of itIn his paper, Monaghan (2010) delves into the intricate relationship between telomeres and life histories, exploring how telomere dynamics influence various aspects of organismal biology, including aging, longevity, and life history traits. Telomeres, the protective caps at the ends of chromosomes, play a crucial role in maintaining genomic stability and regulating cellular lifespan.Monaghan reviews empirical evidence from studies across diverse organisms, from humans to birds and mammals, to elucidate the connections between telomere length, environmental factors, and life history traits such as reproductive strategies and lifespan. He discusses how telomere dynamics can reflect the balance between investment in reproduction and somatic maintenance, influencing evolutionary trade-offs between these competing demands.Full article on https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2010.05705.x
Palacios, J. A., Herranz, D., De Bonis, M. L., Velasco, S., Serrano, M., & Blasco, M. A. (2010). SIRT1 contributes to telomere maintenance and augments global homologous recombination. The Journal of cell biology, 191(7), 1299–1313. https://doi.org/10.1083/jcb.201005160.View Summary –SIRT1 contributes to telomere maintenance and augments global homologous recombinationIn their study, Palacios et al. (2010) investigate the role of the protein SIRT1 in telomere maintenance and DNA repair processes. SIRT1 is a member of the sirtuin family of proteins known for their involvement in various cellular functions, including aging and DNA repair.The researchers demonstrate that SIRT1 contributes to telomere maintenance by promoting the recruitment of telomere-binding proteins and preventing telomere dysfunction. Additionally, they find that SIRT1 enhances global homologous recombination, a DNA repair mechanism crucial for maintaining genomic stability.These findings shed light on the molecular mechanisms underlying telomere maintenance and DNA repair, highlighting the importance of SIRT1 in these processes. The study provides valuable insights into how SIRT1-mediated pathways contribute to cellular homeostasis and genome integrity, with potential implications for aging-related diseases and cancer.Full article on https://rupress.org/jcb/article-abstract/191/7/1299/36318
Wang, Y., Oxer, D., & Hekimi, S. (2015). Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nature communications, 6, 6393. https://doi.org/10.1038/ncomms7393. View Summary –Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesisIn their study, Wang, Oxer, and Hekimi (2015) investigate the relationship between mitochondrial function and lifespan in mice with controlled ubiquinone biosynthesis. Ubiquinone, also known as coenzyme Q10, plays a crucial role in mitochondrial respiration and energy production.The researchers manipulated the biosynthesis of ubiquinone in mice to generate animals with varying levels of this essential cofactor. They found that mice with reduced ubiquinone levels exhibited compromised mitochondrial function, including impaired respiratory chain activity and decreased ATP production. These mice also showed signs of accelerated aging, including reduced lifespan and increased oxidative damage to cellular components.These findings suggest a direct link between mitochondrial function, ubiquinone levels, and lifespan in mice. The study provides valuable insights into the role of mitochondrial function in aging and highlights the potential importance of ubiquinone supplementation in promoting healthy aging.Full article on https://www.nature.com/articles/ncomms7393
Lanza, I. R., & Nair, K. S. (2010). Mitochondrial function as a determinant of life span. Pflugers Archiv: European journal of physiology, 459(2), 277–289. https://doi.org/10.1007/s00424-009-0724-5.View Summary –Mitochondrial function as a determinant of life spanIn their paper, Lanza and Nair (2010) explore the role of mitochondrial function as a determinant of lifespan. Mitochondria are essential organelles involved in energy production, metabolism, and various cellular processes. The authors discuss accumulating evidence suggesting that mitochondrial dysfunction contributes to aging and age-related diseases.The review covers studies examining the relationship between mitochondrial function and lifespan across different organisms, including humans, rodents, and invertebrates. It discusses how alterations in mitochondrial structure, function, and dynamics can impact cellular homeostasis and ultimately influence lifespan.Furthermore, the authors explore potential mechanisms through which mitochondrial function may affect aging, such as oxidative stress, mitochondrial DNA damage, and impaired energy metabolism. They also discuss interventions, such as calorie restriction and exercise, that have been shown to improve mitochondrial function and extend lifespan in experimental models.Full article on https://link.springer.com/article/10.1007/s00424-009-0724-5
Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. doi:10.1016/j.tcb.2014.04.002.View Summary –NAD+ and sirtuins in aging and diseaseIn their review, Imai and Guarente (2014) delve into the roles of nicotinamide adenine dinucleotide (NAD+) and sirtuins in aging and disease. NAD+ is a coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in cellular homeostasis and stress response.The authors discuss how NAD+ levels decline with age and how this reduction is associated with mitochondrial dysfunction, genomic instability, and age-related diseases. They also highlight the importance of sirtuins in mediating the beneficial effects of calorie restriction and exercise on lifespan and healthspan.Furthermore, the review explores emerging evidence suggesting that boosting NAD+ levels or activating sirtuins may have therapeutic potential for treating age-related diseases, including metabolic disorders, neurodegenerative diseases, and cancer.Full article on https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(14)00063-4?elsca1=etoc&elsca2=email&elsca3=0962-8924_201408_24_8_&elsca4=Cell+Press
Tang B. L. (2016). Sirt1 and the Mitochondria. Molecules and cells, 39(2), 87–95. https://doi.org/10.14348/molcells.2016.2318.View Summary –Sirt1 and the MitochondriaIn his paper, Tang (2016) explores the intricate relationship between Sirtuin 1 (Sirt1) and mitochondria, two critical players in cellular homeostasis and longevity. Sirt1 is a member of the sirtuin family of proteins, known for their involvement in various cellular processes, including metabolism, stress response, and aging.Tang discusses the multifaceted roles of Sirt1 in regulating mitochondrial function, dynamics, and biogenesis. Sirt1 has been shown to modulate mitochondrial activity by deacetylating key targets involved in mitochondrial metabolism and oxidative stress response. Additionally, Sirt1 plays a role in regulating mitochondrial dynamics, such as fission and fusion processes, which are essential for maintaining mitochondrial health and function.Furthermore, the paper explores the impact of Sirt1 on mitochondrial biogenesis, the process by which new mitochondria are generated, highlighting its importance in cellular energy production and overall metabolic health.Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757807/
Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007). Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell, 129(3), 473–484. https://doi.org/10.1016/j.cell.2007.03.024.View Summary –Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+In their study, Belenky et al. (2007) investigate the mechanisms through which nicotinamide riboside (NR) promotes lifespan extension via NAD+ metabolism and the sirtuin pathway. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins, such as Sir2, are a family of NAD+-dependent protein deacetylases implicated in aging and longevity.The researchers demonstrate that NR supplementation increases NAD+ levels in yeast and mammalian cells, leading to enhanced Sir2 activity and lifespan extension. They identify the Nrk and Urh1/Pnp1/Meu1 pathways as mediators of NR conversion to NAD+.Furthermore, the study highlights the importance of NAD+ metabolism in regulating sirtuin activity and cellular aging. By modulating NAD+ levels, NR promotes Sir2-mediated gene silencing and enhances lifespan in yeast and Caenorhabditis elegans models.Full article on https://www.cell.com/fulltext/S0092-8674(07)00390-X
Fang, E. F., Kassahun, H., Croteau, D. L., Scheibye-Knudsen, M., Marosi, K., Lu, H., Shamanna, R. A., Kalyanasundaram, S., Bollineni, R. C., Wilson, M. A., Iser, W. B., Wollman, B. N., Morevati, M., Li, J., Kerr, J. S., Lu, Q., Waltz, T. B., Tian, J., Sinclair, D. A., Mattson, M. P., … Bohr, V. A. (2016). NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell metabolism, 24(4), 566–581. https://doi.org/10.1016/j.cmet.2016.09.004.View Summary –NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repairIn their study, Fang et al. (2016) investigate the effects of nicotinamide adenine dinucleotide (NAD+) replenishment on lifespan and healthspan in models of Ataxia Telangiectasia (A-T), a genetic disorder characterized by neurological degeneration and premature aging. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and mitochondrial function.The researchers demonstrate that NAD+ replenishment extends lifespan and improves healthspan in A-T mouse models by promoting mitophagy, the selective degradation of damaged mitochondria, and enhancing DNA repair mechanisms. By boosting NAD+ levels, they observe a reduction in DNA damage accumulation and oxidative stress, leading to improved neuronal function and overall health in A-T mice.Furthermore, the study elucidates the underlying molecular mechanisms through which NAD+ supplementation exerts its beneficial effects, including activation of the SIRT1 pathway, promotion of mitochondrial biogenesis, and enhancement of DNA repair capacity.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30482-X.pdf
Harlan, B. A., Killoy, K. M., Pehar, M., Liu, L., Auwerx, J., & Vargas, M. R. (2020). Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models. Experimental neurology, 327, 113219. https://doi.org/10.1016/j.expneurol.2020.113219.View Summary –Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse modelsIn their study, Harlan et al. (2020) assess the NAD+ biosynthetic pathway in patients with amyotrophic lateral sclerosis (ALS) and investigate the effects of modulating NAD+ levels in mouse models of ALS linked to human superoxide dismutase 1 (hSOD1). ALS is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to muscle weakness and paralysis.The researchers evaluate the NAD+ biosynthetic pathway in ALS patients and find alterations in NAD+ metabolism compared to healthy controls, suggesting dysregulation of NAD+ homeostasis in ALS pathophysiology. They then explore the effects of modulating NAD+ levels through supplementation or genetic manipulation in hSOD1-linked ALS mouse models.Full article on https://www.sciencedirect.com/science/article/pii/S0014488620300509
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., Schoonjans, K., Menzies, K. J., & Auwerx, J. (2016). NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (New York, N.Y.), 352(6292), 1436–1443. https://doi.org/10.1126/science.aaf2693.View Summary –NAD+ repletion improves mitochondrial and stem cell function and enhances life span in miceIn their study, Zhang et al. (2016) investigate the effects of nicotinamide adenine dinucleotide (NAD+) repletion on mitochondrial function, stem cell function, and lifespan in mice. NAD+ is a vital coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The researchers demonstrate that NAD+ repletion through supplementation with its precursor, nicotinamide riboside (NR), enhances mitochondrial function by promoting oxidative metabolism and mitochondrial biogenesis. Additionally, NAD+ supplementation improves stem cell function and enhances tissue regeneration capacity in aged mice.Furthermore, the study reveals that NAD+ repletion extends lifespan in mice, highlighting the potential of targeting NAD+ metabolism as a strategy for promoting healthy aging. The beneficial effects of NAD+ supplementation are attributed to its role in enhancing cellular resilience to stress, promoting tissue repair, and delaying the onset of age-related pathologies.Full article on https://www.science.org/doi/abs/10.1126/science.aaf2693
Peclat, T. R., Thompson, K. L., Warner, G. M., Chini, C., Tarragó, M. G., Mazdeh, D. Z., Zhang, C., Zavala-Solorio, J., Kolumam, G., Liang Wong, Y., Cohen, R. L., & Chini, E. N. (2022). CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging. Aging cell, 21(4), e13589. https://doi.org/10.1111/acel.13589.View Summary –CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological agingIn their study, Peclat et al. (2022) investigate the effects of a CD38 inhibitor, 78c, on lifespan and healthspan in a model of chronological aging in mice. CD38 is an enzyme involved in various cellular processes, including calcium signaling, immune response, and metabolism. It also plays a role in NAD+ metabolism, as it consumes NAD+ during its enzymatic activity.The researchers demonstrate that inhibition of CD38 with 78c extends both lifespan and healthspan in mice undergoing chronological aging. They observe improvements in various health parameters, including metabolic health, immune function, and cognitive function, in mice treated with 78c compared to untreated controls.Furthermore, the study elucidates the underlying mechanisms through which CD38 inhibition exerts its beneficial effects. The researchers find that 78c treatment leads to increased NAD+ levels and activation of the NAD+-dependent enzyme SIRT1, which is known to promote cellular resilience to stress and enhance longevity.Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.13589
Hashimoto, T., Horikawa, M., Nomura, T., & Sakamoto, K. (2010). Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16. Biogerontology, 11(1), 31–43. https://doi.org/10.1007/s10522-009-9225-3.View Summary –Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16In their study, Hashimoto et al. (2010) investigate the effect of nicotinamide adenine dinucleotide (NAD+) on the lifespan of Caenorhabditis elegans, a commonly used model organism for aging research. NAD+ is a coenzyme involved in various cellular processes, including energy metabolism and regulation of gene expression.The researchers demonstrate that supplementation with NAD+ extends the lifespan of C. elegans. They further elucidate the underlying molecular mechanisms by which NAD+ exerts its lifespan-extending effects, focusing on the involvement of two key regulatory genes: sir-2.1 and daf-16.Sir-2.1 is a homolog of the mammalian sirtuin SIRT1, while daf-16 is a FOXO transcription factor involved in the insulin/IGF-1 signaling pathway. Hashimoto et al. show that NAD+ supplementation increases the expression and activity of sir-2.1 and daf-16, leading to enhanced stress resistance and longevity in C. elegans.Full article on https://link.springer.com/article/10.1007/s10522-009-9225-3
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y. S., Viswanathan, M., Schoonjans, K., Guarente, L., & Auwerx, J. (2013). The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell, 154(2), 430–441. https://doi.org/10.1016/j.cell.2013.06.016.View Summary –The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signalingIn their study, Mouchiroud et al. (2013) investigate the role of the nicotinamide adenine dinucleotide (NAD+)/sirtuin pathway in modulating longevity and aging-related processes. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins are a family of NAD+-dependent protein deacetylases that have been implicated in aging and longevity.The researchers demonstrate that activation of the NAD+/sirtuin pathway extends lifespan in model organisms, including Caenorhabditis elegans and Drosophila melanogaster. They elucidate the underlying mechanisms through which NAD+/sirtuin signaling exerts its beneficial effects on longevity.Full article on https://www.cell.com/fulltext/S0092-8674(13)00755-1
Odoh, C. K., Guo, X., Arnone, J. T., Wang, X., & Zhao, Z. K. (2022). The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae. Biogerontology, 23(2), 169–199. https://doi.org/10.1007/s10522-022-09958-x.View Summary –The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiaeIn their study, Odoh et al. (2022) investigate the role of nicotinamide adenine dinucleotide (NAD+) and NAD+ precursors in modulating longevity and lifespan in the budding yeast, Saccharomyces cerevisiae. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The researchers explore the effects of NAD+ and NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), on yeast lifespan using genetic and pharmacological interventions. They demonstrate that supplementation with NAD+ precursors extends the replicative and chronological lifespan of yeast cells.Full article on https://link.springer.com/article/10.1007/s10522-022-09958-x
Sun, N., Youle, R. J., & Finkel, T. (2016). The Mitochondrial Basis of Aging. Molecular cell, 61(5), 654–666. https://doi.org/10.1016/j.molcel.2016.01.028.View Summary –The Mitochondrial Basis of AgingIn their comprehensive review, Sun, Youle, and Finkel (2016) explore the intricate relationship between mitochondria and the aging process. Mitochondria are vital organelles responsible for generating cellular energy and regulating various cellular processes. The review delves into how mitochondrial dysfunction contributes to the aging process at the cellular and organismal levels.The authors discuss several key mechanisms through which mitochondria influence aging, including oxidative stress, mitochondrial DNA (mtDNA) mutations, impaired mitochondrial dynamics, and alterations in mitochondrial metabolism. They highlight the concept of the mitochondrial free radical theory of aging, which proposes that the accumulation of oxidative damage to mtDNA and proteins over time leads to mitochondrial dysfunction and contributes to aging-related decline.Full article on https://www.cell.com/molecular-cell/pdf/S1097-2765(16)00081-2.pdf
Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., Mercken, E. M., Palmeira, C. M., de Cabo, R., Rolo, A. P., Turner, N., Bell, E. L., & Sinclair, D. A. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. https://doi.org/10.1016/j.cell.2013.11.037.View Summary –Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during agingIn their groundbreaking study, Gomes et al. (2013) investigate the role of declining levels of nicotinamide adenine dinucleotide (NAD+) in disrupting nuclear-mitochondrial communication during aging. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The researchers demonstrate that NAD+ levels decline with age in multiple tissues and organisms, including mice and humans. This decline in NAD+ levels leads to impaired mitochondrial function, altered gene expression patterns, and a state of pseudohypoxia, characterized by activation of hypoxia-inducible factor 1-alpha (HIF-1α) signaling.Full article on https://www.cell.com/abstract/S0092-8674%2813%2901521-3?wptouch_preview_theme=enabled
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L. J., Osborne, B., Joshi, S., Lu, Y., Treviño-Villarreal, J. H., Kang, M. J., Hung, T. T., Lee, B., Williams, E. O., Igarashi, M., Mitchell, J. R., Wu, L. E., Turner, N., Arany, Z., … Sinclair, D. A. (2018). Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 173(1), 74–89.e20. https://doi.org/10.1016/j.cell.2018.02.008.View Summary –Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular agingIn their groundbreaking study, Das et al. (2018) investigate the role of an endothelial NAD+-H2S signaling network in vascular aging and explore its potential as a reversible mechanism underlying age-related vascular dysfunction. Endothelial cells play a crucial role in maintaining vascular homeostasis, and dysfunction of these cells is a hallmark of vascular aging and age-related diseases.The researchers demonstrate that impairment of the NAD+-H2S signaling network contributes to vascular aging by promoting endothelial cell senescence and dysfunction. They show that age-related decline in NAD+ levels leads to decreased activity of the enzyme cystathionine gamma-lyase (CSE), which is responsible for generating hydrogen sulfide (H2S) in endothelial cells.Full article on https://www.cell.com/cell/pdf/S0092-8674(18)30152-1.pdf
Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., Bellemin, S., Iyer, S. R., Wang, X., Gariani, K., Sauve, A. A., Cantó, C., Conley, K. E., Walter, L., Lovering, R. M., Chin, E. R., … Auwerx, J. (2016). NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Science translational medicine, 8(361), 361ra139. https://doi.org/10.1126/scitranslmed.aaf5504.View Summary –NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylationIn their study, Ryu et al. (2016) investigate the therapeutic potential of nicotinamide adenine dinucleotide (NAD+) repletion in improving muscle function in muscular dystrophy and countering global poly(ADP-ribosyl)ation (PARylation). Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness and degeneration.The researchers demonstrate that NAD+ repletion improves muscle function in a mouse model of muscular dystrophy. They show that increased NAD+ levels lead to enhanced mitochondrial function, improved muscle strength, and reduced muscle damage and inflammation in dystrophic mice.Furthermore, Ryu et al. elucidate the underlying mechanisms through which NAD+ repletion exerts its beneficial effects on muscle function. They demonstrate that increased NAD+ levels counteract global PARylation, a process associated with DNA damage and impaired muscle function in muscular dystrophy.Full article on https://www.science.org/doi/abs/10.1126/scitranslmed.aaf5504
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., Yoshino, J., & Imai, S. I. (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell metabolism, 24(6), 795–806. https://doi.org/10.1016/j.cmet.2016.09.013.View Summary –Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in miceIn their study, Mills et al. (2016) investigate the effects of long-term administration of nicotinamide mononucleotide (NMN) on age-associated physiological decline in mice. NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The researchers demonstrate that long-term supplementation with NMN mitigates age-related physiological decline in multiple tissues and organs in mice. They show that NMN treatment improves mitochondrial function, enhances oxidative metabolism, and promotes energy expenditure in aged mice.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30495-8.pdf
Lin, J. B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., Yoshino, J., Imai, S. I., & Apte, R. S. (2016). NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice. Cell reports, 17(1), 69–85. https://doi.org/10.1016/j.celrep.2016.08.073.View Summary –NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In MiceIn their study, Lin et al. (2016) investigate the importance of nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) biosynthesis for vision in mice. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The researchers demonstrate that NAMPT-mediated NAD+ biosynthesis is essential for maintaining vision in mice. They show that genetic deletion of Nampt in the retina leads to decreased NAD+ levels, impaired mitochondrial function, and degeneration of photoreceptor cells, resulting in vision loss.Full article on https://www.cell.com/cell-reports/pdf/S2211-1247(16)31169-X.pdf
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., & Suomalainen, A. (2014). Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO molecular medicine, 6(6), 721–731. https://doi.org/10.1002/emmm.201403943.View Summary –Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3In their study, Khan et al. (2014) investigate the efficacy of nicotinamide riboside (NR), a form of vitamin B3, in treating mitochondrial myopathy, a genetic disorder characterized by muscle weakness and fatigue due to dysfunctional mitochondria. Mitochondria are responsible for generating cellular energy, and defects in mitochondrial function can lead to various disorders, including mitochondrial myopathy.The researchers demonstrate that NR supplementation effectively alleviates symptoms of mitochondrial myopathy in a mouse model of the disease. They show that NR treatment increases nicotinamide adenine dinucleotide (NAD+) levels and enhances mitochondrial function in muscle tissues, leading to improved muscle strength and endurance in affected mice.Full article on https://www.embopress.org/doi/abs/10.1002/emmm.201403943
Brown, K. D., Maqsood, S., Huang, J. Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., & Jaffrey, S. R. (2014). Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell metabolism, 20(6), 1059–1068. https://doi.org/10.1016/j.cmet.2014.11.003.View Summary –Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing lossIn their study, Brown et al. (2014) investigate the protective effects of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), on noise-induced hearing loss by activating sirtuin 3 (SIRT3). SIRT3 is a mitochondrial deacetylase known to play a crucial role in protecting against oxidative stress and maintaining mitochondrial function.The researchers demonstrate that NR supplementation activates SIRT3 in the cochlea, the auditory portion of the inner ear, and protects against noise-induced hearing loss in mice. They show that NR treatment increases NAD+ levels and enhances SIRT3 activity, leading to reduced oxidative stress and mitochondrial dysfunction in the cochlea in response to noise exposure.Furthermore, Brown et al. elucidate the underlying mechanisms through which NR-mediated activation of SIRT3 protects against hearing loss. They demonstrate that SIRT3 activation promotes the expression of antioxidant enzymes and reduces the accumulation of reactive oxygen species (ROS) in the cochlea, thereby preserving auditory function and preventing noise-induced damage to hair cells and auditory neurons.Full article on https://www.cell.com/fulltext/S1550-4131(14)00500-2
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell metabolism, 14(4), 528–536. https://doi.org/10.1016/j.cmet.2011.08.014.View Summary –Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in miceIn their study, Yoshino et al. (2011) investigate the therapeutic potential of nicotinamide mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis, in treating the pathophysiology of diet- and age-induced diabetes in mice. NAD+ plays a crucial role in cellular energy metabolism, and its levels decline with aging and in conditions such as diabetes.The researchers demonstrate that NMN supplementation effectively ameliorates glucose intolerance, insulin resistance, and pancreatic β-cell dysfunction in mice fed a high-fat diet or in aged mice. They show that NMN treatment increases NAD+ levels in various tissues, including skeletal muscle, liver, and pancreas, leading to improved glucose metabolism and insulin sensitivity.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(11)00346-9.pdf
Yang, Q., Cong, L., Wang, Y., Luo, X., Li, H., Wang, H., Zhu, J., Dai, S., Jin, H., Yao, G., Shi, S., Hsueh, A. J., & Sun, Y. (2020). Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging. Free radical biology & medicine, 156, 1–10. https://doi.org/10.1016/j.freeradbiomed.2020.05.003.View Summary -In their study, Yang et al. (2020) investigate the role of nicotinamide adenine dinucleotide (NAD+) in ovarian aging and explore the potential therapeutic effects of increasing ovarian NAD+ levels on mitochondrial function and ovarian aging. Ovarian aging is characterized by a decline in ovarian function, including reduced follicle quality and decreased fertility, which are closely associated with mitochondrial dysfunction.The researchers demonstrate that increasing NAD+ levels in the ovaries improves mitochondrial function and reverses ovarian aging in mice. They show that supplementation with nicotinamide riboside (NR), a precursor of NAD+, increases NAD+ levels in ovarian tissues and enhances mitochondrial biogenesis and oxidative phosphorylation, leading to improved follicle quality and ovarian function.Full article on https://www.sciencedirect.com/science/article/pii/S0891584920304214
Roh, E., Myoung Kang, G., Young Gil, S., Hee Lee, C., Kim, S., Hong, D., Hoon Son, G., & Kim, M. S. (2018). Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice. Obesity (Silver Spring, Md.), 26(9), 1448–1456. https://doi.org/10.1002/oby.22263.View Summary –Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese MiceIn their study, Roh et al. (2018) investigate the effects of chronic nicotinamide adenine dinucleotide (NAD+) supplementation on energy metabolism and diurnal rhythm in obese mice. Obesity is associated with dysregulation of energy metabolism and disruptions in circadian rhythms, which can contribute to metabolic dysfunction and weight gain.The researchers demonstrate that chronic NAD+ supplementation improves energy metabolism and restores diurnal rhythm in obese mice. They show that supplementation with nicotinamide riboside (NR), a precursor of NAD+, increases NAD+ levels in various tissues, including adipose tissue, liver, and skeletal muscle, leading to enhanced mitochondrial function and oxidative metabolism.Furthermore, Roh et al. elucidate the underlying mechanisms through which NAD+ supplementation exerts its beneficial effects on energy metabolism and diurnal rhythm. They demonstrate that NR treatment improves insulin sensitivity, reduces adiposity, and increases energy expenditure in obese mice, resulting in improved metabolic health and weight loss.Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/oby.22263
Alegre, J., Rosés, J. M., Javierre, C., Ruiz-Baqués, A., Segundo, M. J., & de Sevilla, T. F. (2010). Nicotinamida adenina dinucleótido (NADH) en pacientes con síndrome de fatiga crónica [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. Revista clinica espanola, 210(6), 284–288. https://doi.org/10.1016/j.rce.2009.09.015.View Summary –Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndromeIn their study, Alegre et al. (2010) investigate the potential therapeutic effects of nicotinamide adenine dinucleotide (NADH) supplementation in patients with chronic fatigue syndrome (CFS). Chronic fatigue syndrome is a complex disorder characterized by severe fatigue that is not alleviated by rest and is accompanied by various other symptoms, including cognitive impairment, sleep disturbances, and muscle pain.The researchers conducted a clinical trial to evaluate the efficacy of NADH supplementation in alleviating symptoms and improving quality of life in patients with CFS. They administered NADH orally to patients with CFS and assessed various outcome measures, including fatigue severity, cognitive function, and overall well-being.Full article on https://europepmc.org/article/med/20447621
Dehhaghi, M., Panahi, H., Kavyani, B., Heng, B., Tan, V., Braidy, N., & Guillemin, G. J. (2022). The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Aging and disease, 13(3), 698–711. https://doi.org/10.14336/AD.2021.0824.View Summary –The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue SyndromeIn their study, Dehhaghi et al. (2022) explore the role of the kynurenine pathway and nicotinamide adenine dinucleotide (NAD+) metabolism in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition characterized by persistent fatigue, cognitive impairment, and other symptoms that significantly impair daily functioning.The researchers conducted a comprehensive review of the literature to examine the involvement of the kynurenine pathway and NAD+ metabolism in the pathophysiology of ME/CFS. They discuss the dysregulation of the kynurenine pathway, which leads to increased production of neurotoxic metabolites such as quinolinic acid and kynurenine, and its potential contribution to neuroinflammation, oxidative stress, and mitochondrial dysfunction observed in ME/CFS patients.Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116917/
Castro-Marrero, J., Segundo, M. J., Lacasa, M., Martinez-Martinez, A., Sentañes, R. S., & Alegre-Martin, J. (2021). Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 13(8), 2658. https://doi.org/10.3390/nu13082658.View Summary –Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled TrialIn their study, Castro-Marrero et al. (2021) investigate the effect of dietary supplementation with coenzyme Q10 (CoQ10) plus nicotinamide adenine dinucleotide (NADH) on fatigue perception and health-related quality of life in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a complex and debilitating condition characterized by persistent fatigue, cognitive impairment, and other symptoms that significantly impair daily functioning.The researchers conducted a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of CoQ10 plus NADH supplementation in individuals with ME/CFS. Participants were randomly assigned to receive either CoQ10 plus NADH or placebo for a specified duration, and various outcome measures, including fatigue perception and health-related quality of life, were assessed before and after supplementation.Full article on https://www.mdpi.com/2072-6643/13/8/2658
Castro-Marrero, J., Sáez-Francàs, N., Segundo, M. J., Calvo, N., Faro, M., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2016). Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial. Clinical nutrition (Edinburgh, Scotland), 35(4), 826–834. https://doi.org/10.1016/j.clnu.2015.07.010.View Summary –Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trialIn their study, Castro-Marrero et al. (2016) investigate the effect of supplementation with coenzyme Q10 (CoQ10) plus nicotinamide adenine dinucleotide (NADH) on maximum heart rate after exercise testing in individuals with chronic fatigue syndrome (CFS). CFS is a debilitating condition characterized by persistent fatigue, post-exertional malaise, and other symptoms that significantly impact daily functioning.The researchers conducted a randomized, controlled, double-blind trial to assess the impact of CoQ10 plus NADH supplementation on maximum heart rate following exercise testing in individuals with CFS. Participants were randomly assigned to receive either CoQ10 plus NADH or placebo for a specified duration, and their maximum heart rates during exercise testing were measured before and after supplementation.Full article on https://www.sciencedirect.com/science/article/pii/S0261561415001892
Castro-Marrero, J., Cordero, M. D., Segundo, M. J., Sáez-Francàs, N., Calvo, N., Román-Malo, L., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2015). Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?. Antioxidants & redox signaling, 22(8), 679–685. https://doi.org/10.1089/ars.2014.6181.View Summary +
Mach, J., Midgley, A. W., Dank, S., Grant, R. S., & Bentley, D. J. (2010). The effect of antioxidant supplementation on fatigue during exercise: potential role for NAD+(H). Nutrients, 2(3), 319–329. https://doi.org/10.3390/nu2030319.View Summary –The Effect of Antioxidant Supplementation on Fatigue during Exercise: Potential Role for NAD+(H)In their study, Mach et al. (2010) explored the potential role of antioxidant supplementation, particularly nicotinamide adenine dinucleotide (NAD^+(H)), in mitigating fatigue during exercise. Fatigue during exercise can stem from various factors, including oxidative stress, which can compromise cellular function and energy production.The researchers conducted a study to investigate whether antioxidant supplementation, with a focus on NAD^+(H), could influence fatigue levels during exercise. Participants were provided with antioxidant supplements containing NAD^+(H) or a placebo before engaging in exercise sessions. The effects of supplementation on fatigue perception and exercise performance were then evaluated.Full article on https://www.mdpi.com/2072-6643/2/3/319
Santaella, M. L., Font, I., & Disdier, O. M. (2004). Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. Puerto Rico health sciences journal, 23(2), 89–93.View Summary +
Stein LR, Imai S. The dynamic regulation of NAD metabolism in mitochondria. Trends EndocrinolMetab. 2012;23(9):420-428. doi:10.1016/j.tem.2012.06.005.View Summary –The dynamic regulation of NAD metabolism in mitochondriaIn their review article, Stein and Imai (2012) provide insights into the dynamic regulation of nicotinamide adenine dinucleotide (NAD) metabolism within mitochondria, focusing on its significance in cellular physiology and metabolic homeostasis. NAD is a crucial coenzyme involved in various metabolic processes, including energy production, redox reactions, and gene expression regulation.The authors discuss the importance of NAD metabolism in maintaining mitochondrial function and cellular health. Mitochondria play a central role in energy production through oxidative phosphorylation, where NAD is essential for the electron transport chain and ATP synthesis. Additionally, NAD serves as a substrate for various enzymes, including sirtuins, which regulate cellular processes such as gene expression, DNA repair, and apoptosis.The review highlights the dynamic regulation of NAD levels within mitochondria, which can be influenced by factors such as nutrient availability, cellular stress, and aging. Alterations in NAD metabolism have been implicated in various age-related diseases, including metabolic disorders, neurodegenerative diseases, and cancer.Full article on https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(12)00106-3
Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11(9):535-546. doi:10.1038/nrendo.2015.117.View Summary –Physiological and pathophysiological roles of NAMPT and NAD metabolismIn their review published in Nature Reviews Endocrinology, Garten et al. (2015) explore the physiological and pathophysiological roles of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) metabolism. NAD is a crucial cofactor involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.The authors discuss the multifaceted roles of NAMPT, the rate-limiting enzyme in the salvage pathway of NAD synthesis. NAMPT catalyzes the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN), a key step in NAD biosynthesis. They highlight the importance of NAMPT-mediated NAD synthesis in maintaining cellular redox balance, mitochondrial function, and metabolic homeostasis.Garten et al. delve into the diverse functions of NAD-dependent enzymes, including sirtuins, poly(ADP-ribose) polymerases (PARPs), and cyclic ADP-ribose synthases (CD38 and CD157), in regulating cellular processes such as transcription, DNA repair, and calcium signaling. They discuss how alterations in NAD metabolism and dysregulation of NAD-dependent pathways contribute to the pathogenesis of various diseases, including metabolic disorders, neurodegenerative diseases, cancer, and aging.Full article on https://www.nature.com/articles/nrendo.2015.117
Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice. Front Pharmacol. 2016;7:258. Published 2016 Aug 19. doi:10.3389/fphar.2016.00258.View Summary +
Rappou E, Jukarainen S, Rinnankoski-Tuikka R et al (2016) Weight loss is associated with increased NAD+/SIRT1 expression but reduced PARP activity in white adipose tissue. J ClinEndocrinolMetab 101(3):1263–1273. https://doi.org/10.1210/jc.2015-3054. View Summary +
Cantó C, Houtkooper RH, Pirinen E, et al. The NAD(+) precursor nicotinamideriboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-847. doi:10.1016/j.cmet.2012.04.022.View Summary +
Crisol BM, Veiga CB, Lenhare L, et al. Nicotinamideriboside induces a thermogenic response in lean mice. Life Sci. 2018;211:1-7. doi:10.1016/j.lfs.2018.09.015.View Summary +
Jukarainen S, Heinonen S, Rämö JT, et al. Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins. J ClinEndocrinolMetab. 2016;101(1):275-283. doi:10.1210/jc.2015-3095.View Summary –Obesity Is Associated With Low NAD+/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic TwinsThe study by Jukarainen et al., titled “Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins,” investigated the expression levels of the NAD(+)/SIRT pathway in adipose tissue of monozygotic twins who were discordant for body mass index (BMI).In this study, the researchers compared the expression levels of genes related to the NAD(+)/SIRT pathway in adipose tissue samples obtained from BMI-discordant monozygotic twins. They found that twins with obesity had lower expression levels of genes involved in the NAD(+)/SIRT pathway compared to their lean counterparts. Specifically, they observed decreased expression of nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD(+) biosynthesis, as well as reduced expression of sirtuin 1 (SIRT1), a key regulator of cellular metabolism and energy homeostasis.Full article on https://academic.oup.com/jcem/article-abstract/101/1/275/2806840
Yamaguchi S, Yoshino J. Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy. Bioessays. 2017;39(5):10.1002/bies.201600227. doi:10.1002/bies.201600227.View Summary –Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapyIn the article “Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy” by Yamaguchi and Yoshino, the authors delve into the intricate relationship between adipose tissue NAD(+) levels, obesity, and insulin resistance, offering insights into potential therapeutic avenues.They elucidate how dysregulation of NAD(+) metabolism in adipose tissue can contribute to the pathogenesis of obesity and insulin resistance. Specifically, they discuss the role of NAD(+) in regulating key metabolic processes such as mitochondrial function, adipogenesis, and inflammation.The authors highlight the importance of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD(+) salvage pathway, in maintaining NAD(+) levels and metabolic homeostasis in adipose tissue. They also explore the impact of NAD(+) precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), on adipose tissue metabolism and insulin sensitivity.Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/bies.201600227
Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD (+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528–536. doi: 10.1016/j.cmet.2011.08.014.View Summary +
Trammell SA, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, Obrosov A, Kardon RH, Yorek MA, Brenner C. Nicotinamideriboside opposes type 2 diabetes and neuropathy in mice. Sci Rep. 2016;6:26933. doi: 10.1038/srep26933.View Summary +
Frederick DW, Davis JG, Davila A, Jr, Agarwal B, Michan S, Puchowicz MA, Nakamaru-Ogiso E, Baur JA. Increasing NAD synthesis in muscle via nicotinamidephosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem. 2015;290(3):1546–1558. doi: 10.1074/jbc.M114.579565.View Summary –Increasing NAD synthesis in muscle via nicotinamidephosphoribosyltransferase is not sufficient to promote oxidative metabolismIn their 2015 study published in the Journal of Biological Chemistry, Frederick et al. investigated the effects of increasing nicotinamide adenine dinucleotide (NAD) synthesis in muscle through nicotinamide phosphoribosyltransferase (NAMPT) overexpression on oxidative metabolism.The researchers conducted experiments using transgenic mice with muscle-specific overexpression of NAMPT, the rate-limiting enzyme in the NAD salvage pathway. They examined the impact of NAMPT overexpression on mitochondrial function, oxidative metabolism, and metabolic adaptation in muscle tissue.Contrary to expectations, the study findings revealed that increasing NAD synthesis via NAMPT overexpression in muscle did not promote oxidative metabolism or mitochondrial biogenesis. Despite elevated NAD levels, the NAMPT-overexpressing mice exhibited impaired mitochondrial function, reduced mitochondrial DNA content, and diminished expression of genes involved in mitochondrial biogenesis and oxidative metabolism.Full article on https://www.jbc.org/article/S0021-9258(20)57813-7/abstract
Sasaki T, Kikuchi O, Shimpuku M, Susanti VY, Yokota-Hashimoto H, Taguchi R, Shibusawa N, Sato T, et al. Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. Diabetologia. 2014;57(4):819–831. doi: 10.1007/s00125-013-3140-5.View Summary –Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in miceIn their 2014 study published in Diabetologia, Sasaki et al. investigated the role of hypothalamic SIRT1 in preventing age-associated weight gain by improving leptin sensitivity in mice.The researchers focused on SIRT1, a protein involved in various cellular processes including metabolism, aging, and energy homeostasis. They hypothesized that SIRT1 in the hypothalamus, a key brain region regulating energy balance, might play a role in age-related changes in body weight and metabolism.To test their hypothesis, the researchers conducted experiments using mice with specific deletion of SIRT1 in the hypothalamus. They assessed the effects of hypothalamic SIRT1 deletion on age-associated changes in body weight, energy expenditure, food intake, and leptin sensitivity.Full article on https://link.springer.com/article/10.1007/s00125-013-3140-5
Yamaguchi S, Franczyk MP, Chondronikola M, et al. Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice. ProcNatlAcadSci U S A. 2019;116(47):23822-23828. doi:10.1073/pnas.1909917116.View Summary –Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in miceIn their 2019 study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), Yamaguchi et al. investigated the role of adipose tissue NAD+ biosynthesis in regulating adaptive thermogenesis and whole-body energy homeostasis in mice.The researchers focused on NAD+ biosynthesis, a critical process involved in cellular metabolism and energy production. They hypothesized that NAD+ biosynthesis in adipose tissue might play a role in regulating adaptive thermogenesis, a process by which the body generates heat in response to cold or excess energy intake.To test their hypothesis, the researchers utilized genetically modified mice with adipose tissue-specific deletion of an enzyme involved in NAD+ biosynthesis, namely nicotinamide phosphoribosyltransferase (Nampt). They compared these mice with control mice under various experimental conditions, including exposure to cold temperatures and high-fat diet feeding.Full article on https://www.pnas.org/doi/abs/10.1073/pnas.1909917116
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., et al. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 24, 795–806. doi: 10.1016/j.cmet.2016.09.013.View Summary +
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022.View Summary +
Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., Mercken, E. M., Palmeira, C. M., de Cabo, R., Rolo, A. P., Turner, N., Bell, E. L., & Sinclair, D. A. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. https://doi.org/10.1016/j.cell.2013.11.037.View Summary –Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during agingIn their 2013 study published in Cell, Gomes et al. investigated the role of declining nicotinamide adenine dinucleotide (NAD+) levels in the aging process, particularly its impact on nuclear-mitochondrial communication and cellular metabolism.The researchers aimed to understand how declining NAD+ levels contribute to age-related physiological decline and dysfunction. They hypothesized that decreased NAD+ availability disrupts the balance between nuclear and mitochondrial functions, leading to a “pseudohypoxic” state resembling cellular responses to low oxygen levels.To investigate this hypothesis, the researchers conducted experiments using various cell culture models and mouse models with altered NAD+ levels. They measured cellular oxygen consumption rates, gene expression patterns, and metabolic parameters to assess the effects of NAD+ depletion on cellular metabolism and mitochondrial function.Full article on https://www.cell.com/fulltext/S1550-4131(12)00192-1
Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018;8:622. Published 2018 Dec 12. doi:10.3389/fonc.2018.00622.View Summary –NAD Metabolism in Cancer TherapeuticsIn their 2018 review published in Frontiers in Oncology, Yaku et al. explored the intricate relationship between nicotinamide adenine dinucleotide (NAD+) metabolism and cancer therapeutics. They discussed how cancer cells exhibit alterations in NAD+ metabolism, including changes in biosynthesis, consumption, and compartmentalization, which contribute to their proliferation, survival, and metastasis. The authors highlighted the role of NAD+-consuming enzymes such as PARPs and sirtuins in cancer development and progression, and they discussed therapeutic strategies targeting NAD+ metabolism, including inhibition of biosynthesis and modulation of NAD+-consuming enzymes. These approaches aim to exploit the vulnerabilities of cancer cells related to their altered NAD+ metabolism, offering potential opportunities for novel cancer therapies. The review also discussed the clinical implications of targeting NAD+ metabolism, showcasing the potential of compounds like PARP inhibitors and sirtuin modulators in preclinical and clinical cancer studies.Full article on https://www.frontiersin.org/articles/10.3389/fonc.2018.00622/full
Lewis JE, Singh N, Holmila RJ, et al. Targeting NAD+ Metabolism to Enhance Radiation Therapy Responses. SeminRadiatOncol. 2019;29(1):6-15. doi:10.1016/j.semradonc.2018.10.009.View Summary –Targeting NAD+ Metabolism to Enhance Radiation Therapy ResponsesIn their 2019 article published in Seminars in Radiation Oncology, Lewis et al. delved into the potential of targeting nicotinamide adenine dinucleotide (NAD+) metabolism to augment responses to radiation therapy. The authors explored the intricate interplay between NAD+ metabolism and the cellular response to radiation, emphasizing how alterations in NAD+ levels impact DNA repair mechanisms, cell survival pathways, and tumor microenvironment dynamics. They discussed various strategies aimed at modulating NAD+ metabolism, such as targeting NAD+ biosynthesis pathways, inhibiting NAD+-consuming enzymes like PARPs, and enhancing NAD+ salvage pathways. Through a comprehensive review of preclinical studies and clinical trials, the authors highlighted the promising therapeutic potential of combining radiation therapy with NAD+ metabolism-targeting agents to improve treatment outcomes for cancer patients.Full article on https://www.sciencedirect.com/science/article/pii/S1053429618300900
Djouder N. Boosting NAD(+) for the prevention and treatment of liver cancer. Mol Cell Oncol. 2015;2(4):e1001199. Published 2015 Feb 3. doi:10.1080/23723556.2014.1001199.View Summary –Boosting NAD+ for the prevention and treatment of liver cancerIn the 2015 article published in Molecular and Cellular Oncology, Djouder explored the potential of boosting nicotinamide adenine dinucleotide (NAD+) levels for the prevention and treatment of liver cancer. The author discussed how dysregulation of NAD+ metabolism contributes to the pathogenesis of liver cancer, highlighting its role in maintaining cellular homeostasis, regulating energy metabolism, and modulating various signaling pathways involved in cancer progression. Djouder also reviewed preclinical studies demonstrating the efficacy of NAD+-boosting interventions, such as supplementation with NAD+ precursors or inhibition of NAD+-consuming enzymes, in suppressing liver tumorigenesis and improving therapeutic responses. By shedding light on the intricate interplay between NAD+ metabolism and liver cancer biology, the article provided valuable insights into the development of novel preventive and therapeutic strategies targeting this metabolic pathway.Full article on https://www.tandfonline.com/doi/abs/10.1080/23723556.2014.1001199
Elhassan YS, Kluckova K, Fletcher RS, et al. NicotinamideRiboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. doi:10.1016/j.celrep.2019.07.043.View Summary –NicotinamideRiboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory SignaturesIn their 2019 study published in Cell Reports, Elhassan and colleagues investigated the effects of nicotinamide riboside (NR) supplementation on the aged human skeletal muscle nicotinamide adenine dinucleotide (NAD+) metabolome and its associated transcriptomic and anti-inflammatory signatures. Through a randomized controlled trial involving older adults, the researchers demonstrated that NR supplementation augmented the NAD+ metabolome in skeletal muscle tissue. Furthermore, NR treatment induced transcriptomic changes indicative of improved mitochondrial function and anti-inflammatory responses in skeletal muscle. These findings suggest that NR supplementation holds promise as a potential intervention to counteract age-related declines in skeletal muscle function and promote overall health in older individuals.Full article on https://www.cell.com/cell-reports/pdf/S2211-1247(19)30940-4.pdf
Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels. Rejuvenation Res. 2014;17(1):62-69. doi:10.1089/rej.2014.1546.View Summary –Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levelsIn their 2014 study published in Rejuvenation Research, Mendelsohn and Larrick investigated the potential of restoring normal nicotinamide adenine dinucleotide (NAD⁺) levels to partially reverse skeletal muscle aging. They examined the effects of NAD⁺ supplementation on age-related declines in skeletal muscle function. Their findings suggested that restoring normal NAD⁺ levels could partially reverse some aspects of skeletal muscle aging, indicating a potential therapeutic approach for mitigating age-related muscle decline.Full article on https://www.liebertpub.com/doi/abs/10.1089/rej.2014.1546
Goody MF, Henry CA. A need for NAD+ in muscle development, homeostasis, and aging. Skelet Muscle. 2018;8(1):9. Published 2018 Mar 7. doi:10.1186/s13395-018-0154-1.View Summary –A need for NAD+ in muscle development, homeostasis, and agingIn their 2018 review published in Skeletal Muscle, Goody and Henry underscored the essential role of nicotinamide adenine dinucleotide (NAD⁺) in muscle development, homeostasis, and aging. They discussed the importance of NAD⁺ as a coenzyme involved in various cellular processes critical for muscle function, including energy metabolism, mitochondrial biogenesis, and stress response pathways. Additionally, they highlighted emerging evidence suggesting that dysregulation of NAD⁺ metabolism may contribute to age-related muscle decline and proposed NAD⁺ supplementation as a potential strategy to promote muscle health and combat aging-related muscle dysfunction.Full article on https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0154-1
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019). NAD+ in Brain Aging and Neurodegenerative Disorders. Cell metabolism, 30(4), 630–655. https://doi.org/10.1016/j.cmet.2019.09.001.View Summary –NAD+ in Brain Aging and Neurodegenerative DisordersIn their comprehensive review published in Cell Metabolism in 2019, Lautrup et al. explored the role of nicotinamide adenine dinucleotide (NAD⁺) in brain aging and neurodegenerative disorders. The authors discussed how NAD⁺ levels decline with age and how this decline contributes to various aspects of brain aging, including mitochondrial dysfunction, oxidative stress, impaired DNA repair, and dysregulated calcium homeostasis. They also examined the potential therapeutic implications of boosting NAD⁺ levels through supplementation or activation of NAD⁺-dependent enzymes, such as sirtuins and PARPs, in mitigating age-related cognitive decline and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Additionally, the review highlighted ongoing research efforts aimed at understanding the mechanisms underlying NAD⁺ metabolism in the brain and its impact on neuronal function and survival.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(19)30502-9.pdf
Mao, K., & Zhang, G. (2022). The role of PARP1 in neurodegenerative diseases and aging. The FEBS journal, 289(8), 2013–2024. https://doi.org/10.1111/febs.15716.View Summary –The role of PARP1 in neurodegenerative diseases and agingIn their article published in The FEBS Journal in 2022, Mao and Zhang explored the role of poly(ADP-ribose) polymerase 1 (PARP1) in neurodegenerative diseases and aging. The authors discussed how PARP1, a nuclear enzyme involved in DNA repair and transcriptional regulation, is implicated in various neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. They reviewed evidence suggesting that PARP1 activation contributes to neuronal dysfunction and death through multiple mechanisms, including DNA damage accumulation, mitochondrial dysfunction, inflammation, and impaired autophagy. Additionally, the authors discussed the potential therapeutic strategies targeting PARP1 in these diseases, highlighting PARP inhibitors as promising candidates for intervention. Overall, the article provides insights into the multifaceted roles of PARP1 in neurodegeneration and aging, emphasizing its potential as a therapeutic target for mitigating age-related neurodegenerative disorders.Full article on https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15716
Ying W. (2007). NAD+ and NADH in brain functions, brain diseases and brain aging. Frontiers in bioscience: a journal and virtual library, 12, 1863–1888. https://doi.org/10.2741/2194.View Summary –NAD+ and NADH in brain functions, brain diseases and brain agingIn the 2007 article “NAD+ and NADH in brain functions, brain diseases, and brain aging” published in Frontiers in Bioscience, Ying delves into the crucial roles of nicotinamide adenine dinucleotide (NAD+) and its reduced form, NADH, in various aspects of brain function, pathology, and aging. The author comprehensively discusses the involvement of NAD+ and NADH in energy metabolism, redox reactions, and signaling pathways within the brain. Moreover, the article explores the implications of dysregulated NAD+ metabolism in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as in brain aging processes. By examining the molecular mechanisms underlying NAD+ and NADH actions, Ying sheds light on their potential as therapeutic targets for addressing brain-related disorders and age-related cognitive decline.Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Lloret, A., & Beal, M. F. (2019). PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochemical research, 44(10), 2423–2434. https://doi.org/10.1007/s11064-019-02809-1.View Summary –PGC-1α, sirtuins and PARPs in Huntington’s disease and other neurodegenerative conditions: NAD+ to rule them allIn their 2019 paper titled “PGC-1α, Sirtuins, and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All,” Lloret and Beal explore the roles of PGC-1α, sirtuins, and PARPs in Huntington’s disease (HD) and other neurodegenerative conditions, emphasizing the pivotal role of nicotinamide adenine dinucleotide (NAD+) in these pathways. The authors discuss how dysregulation of these key regulators contributes to mitochondrial dysfunction, oxidative stress, and neuroinflammation observed in HD and other neurodegenerative diseases. They highlight the therapeutic potential of NAD+ augmentation strategies in mitigating disease progression by restoring cellular homeostasis and promoting neuroprotection. This review provides valuable insights into the interconnected pathways involving PGC-1α, sirtuins, and PARPs, underscoring NAD+ as a central player in the pathophysiology and potential treatment of neurodegenerative conditions.Full article on https://link.springer.com/article/10.1007/s11064-019-02809-1
Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130(6):1095-1107. doi:10.1016/j.cell.2007.07.035.View Summary –Nutrient-sensitive mitochondrial NAD+ levels dictate cell survivalIn their 2007 study published in Cell, titled “Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival,” Yang et al. investigate the role of mitochondrial nicotinamide adenine dinucleotide (NAD+) levels in cell survival. They demonstrate that mitochondrial NAD+ levels play a critical role in determining cell fate under conditions of nutrient deprivation and stress. The researchers show that maintenance of mitochondrial NAD+ levels through nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis is essential for cell survival during energy stress. Furthermore, they highlight the importance of the NAD+-dependent enzyme sirtuin 3 (SIRT3) in protecting cells from metabolic stress-induced apoptosis by promoting mitochondrial function and antioxidant defense. Overall, this study underscores the significance of mitochondrial NAD+ metabolism in cellular responses to nutrient availability and stress, providing insights into potential therapeutic strategies for conditions associated with metabolic dysregulation.Full article on https://www.cell.com/fulltext/S0092-8674(07)00973-7
Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-1213. doi:10.1126/science.aac4854.View Summary –NAD+ in aging, metabolism, and neurodegenerationIn his 2015 review article published in Science titled “NAD⁺ in aging, metabolism, and neurodegeneration,” Verdin explores the multifaceted roles of nicotinamide adenine dinucleotide (NAD⁺) in various physiological processes. He discusses how NAD⁺ serves as a cofactor for enzymes involved in diverse cellular functions, including metabolism, DNA repair, and gene expression regulation. Verdin highlights emerging evidence implicating NAD⁺ dysregulation in aging-related decline and age-associated diseases, such as neurodegenerative disorders. He further examines the therapeutic potential of targeting NAD⁺ metabolism to ameliorate age-related pathologies, suggesting that interventions aimed at boosting NAD⁺ levels could have beneficial effects on healthspan and lifespan. Overall, this review underscores the importance of NAD⁺ as a central regulator of cellular metabolism and aging processes, providing insights into potential strategies for mitigating age-related decline and disease.Full article on https://www.science.org/doi/abs/10.1126/science.aac4854
Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888. Published 2007 Jan 1. doi:10.2741/2194.View Summary –NAD+ and NADH in brain functions, brain diseases and brain agingIn the comprehensive review article “NAD+ and NADH in brain functions, brain diseases, and brain aging,” published in Frontiers in Bioscience in 2007, Ying W. delves into the intricate roles of nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH) in brain physiology and pathology. The review elucidates how NAD+ and NADH serve as crucial cofactors in numerous enzymatic reactions involved in energy metabolism, neurotransmitter synthesis, and antioxidant defense mechanisms within the brain. Furthermore, Ying W. explores the implications of alterations in NAD+ and NADH levels in various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and ischemic brain injury. The review also discusses the potential impact of NAD+ metabolism on neuronal survival and aging processes in the brain. Overall, this comprehensive review sheds light on the multifaceted roles of NAD+ and NADH in brain function and dysfunction, offering valuable insights into their therapeutic potential for treating brain-related disorders and promoting healthy brain aging.Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C. Nicotinamideriboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell. 2007 May 4;129(3):473-84.View Summary +
Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547. doi:10.1016/j.cmet.2018.02.011.View Summary +
Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi:10.1371/journal.pone.0042357.View Summary –Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human TissueIn their study published in PLoS One in 2012, Massudi et al. investigate age-associated alterations in oxidative stress and NAD+ metabolism across various human tissues. The researchers examined the levels of oxidative stress markers and NAD+ metabolites in samples from different age groups, aiming to elucidate potential links between these changes and aging. Their findings reveal significant increases in oxidative stress markers and declines in NAD+ levels with advancing age, suggesting a potential interplay between oxidative stress and NAD+ metabolism in the aging process. This study contributes valuable insights into the molecular mechanisms underlying age-related changes in cellular function and highlights the importance of NAD+ metabolism as a potential target for interventions aimed at mitigating age-related decline.Full article on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042357
Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. ExpGerontol. 2020;132:110831. doi:10.1016/j.exger.2020.110831.View Summary –NAD+ therapy in age-related degenerative disorders: A benefit/risk analysisIn their review article published in Experimental Gerontology in 2020, Braidy and Liu conducted a benefit/risk analysis of NAD+ therapy in age-related degenerative disorders. They synthesized existing evidence on the potential benefits and risks of NAD+ supplementation in various age-related conditions, including neurodegenerative diseases, metabolic disorders, and cardiovascular diseases. The authors evaluated the preclinical and clinical studies investigating the efficacy and safety of NAD+ therapy, considering factors such as dosing regimens, treatment duration, and adverse effects. Their analysis provides valuable insights into the therapeutic potential of NAD+ supplementation across different age-related degenerative disorders while highlighting the need for further research to optimize treatment strategies and minimize potential risks.Full article on https://www.sciencedirect.com/science/article/pii/S0531556519307582
Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It’s Destroyed. Cell Metab. 2016;23(6):965-966. doi:10.1016/j.cmet.2016.05.022.View Summary –Why NAD(+) Declines during Aging: It’s DestroyedIn their review published in Cell Metabolism in 2016, Schultz and Sinclair explored the mechanisms underlying the decline of NAD+ during aging, proposing that it is primarily due to its degradation. They highlighted the importance of understanding the factors contributing to NAD+ depletion in aging cells and tissues, including increased activity of NAD+-consuming enzymes such as PARPs and sirtuins, as well as decreased NAD+ biosynthesis. The authors discussed how this decline in NAD+ levels can lead to impaired cellular functions and contribute to the development of age-related diseases. Their insights shed light on potential strategies to counteract NAD+ decline and mitigate age-related health decline.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30244-3.pdf
Yaku K, Okabe K, Nakagawa T. NAD metabolism: Implications in aging and longevity. Ageing Res Rev. 2018;47:1-17. doi:10.1016/j.arr.2018.05.006.View Summary –NAD metabolism: Implications in aging and longevityIn their review published in Ageing Research Reviews in 2018, Yaku, Okabe, and Nakagawa discussed the implications of NAD metabolism in aging and longevity. They provided insights into the role of NAD in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. The authors highlighted the decline in NAD levels during aging and its association with age-related diseases. They also discussed the potential of NAD precursors and NAD-boosting molecules as therapeutic interventions to promote healthy aging and extend lifespan. Their comprehensive review contributes to our understanding of the intricate relationship between NAD metabolism and the aging process.Full article on https://www.sciencedirect.com/science/article/pii/S1568163718300060
Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi:10.1016/j.cmet.2015.05.023.View Summary –NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the NucleusIn their review published in Cell Metabolism in 2015, Cantó, Menzies, and Auwerx explored the intricate interplay between NAD(+) metabolism and the regulation of energy homeostasis. They discussed how NAD(+) serves as a crucial cofactor in various metabolic pathways, including glycolysis, oxidative phosphorylation, and fatty acid oxidation, thereby influencing cellular energy production. The authors also highlighted the role of NAD(+) in modulating mitochondrial function, biogenesis, and dynamics, as well as its involvement in nuclear processes such as transcriptional regulation and DNA repair. They emphasized the importance of maintaining NAD(+) homeostasis for overall metabolic health and proposed NAD(+) modulation as a potential therapeutic strategy for metabolic disorders. This comprehensive review provides valuable insights into the multifaceted roles of NAD(+) in energy metabolism and its implications for metabolic homeostasis.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(15)00266-1.pdf
Zhang N, Sauve AA. Regulatory Effects of NAD+ Metabolic Pathways on Sirtuin Activity. ProgMolBiolTransl Sci. 2018;154:71-104. doi:10.1016/bs.pmbts.2017.11.012.View Summary –Regulatory effects of NAD+ metabolic pathways on sirtuin activityIn their publication in Progress in Molecular Biology and Translational Science in 2018, Zhang and Sauve delved into the regulatory effects of NAD+ metabolic pathways on sirtuin activity. They discussed how sirtuins, a class of NAD+-dependent protein deacylases, play critical roles in various cellular processes such as metabolism, stress response, and aging. The authors explored the intricate interplay between NAD+ availability and sirtuin function, highlighting how changes in NAD+ levels can modulate sirtuin activity and subsequently impact cellular physiology. They also discussed the regulatory mechanisms governing NAD+ biosynthesis, salvage, and consumption, shedding light on the complex network of pathways that govern cellular NAD+ metabolism. Through their comprehensive review, Zhang and Sauve provided valuable insights into the tight coupling between NAD+ metabolism and sirtuin-mediated signaling, with implications for understanding cellular homeostasis and disease pathogenesis.Full article on https://www.sciencedirect.com/science/article/pii/S1877117317301904
Connell, N.J., Houtkooper, R.H. &Schrauwen, P. NAD+ metabolism as a target for metabolic health: have we found the silver bullet?.Diabetologia 62, 888–899 (2019). https://doi.org/10.1007/s00125-019-4831-3.View Summary –NAD+ metabolism as a target for metabolic health: have we found the silver bullet?In their review article published in Diabetologia in 2019, Connell et al. examined NAD+ metabolism as a potential target for improving metabolic health, questioning whether it could serve as a “silver bullet” in addressing metabolic disorders. They synthesized findings from various studies exploring the role of NAD+ in cellular metabolism, mitochondrial function, and aging-related processes. The authors discussed how alterations in NAD+ levels and its related pathways are implicated in metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disorders. Additionally, they evaluated emerging therapeutic strategies aimed at modulating NAD+ metabolism, including the use of NAD+ precursors and activators of NAD+-dependent enzymes like sirtuins. Connell and colleagues critically assessed the current state of research in this field, highlighting both the promises and challenges associated with targeting NAD+ metabolism for metabolic health interventions. Their comprehensive review provides valuable insights into the potential of NAD+ modulation as a therapeutic avenue for metabolic disorders.Full article on https://link.springer.com/article/10.1007/s00125-019-4831-3
Elhassan YS, Philp AA, Lavery GG. Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule. J Endocr Soc. 2017;1(7):816-835. Published 2017 May 15. doi:10.1210/js.2017-00092.View Summary –Targeting NAD+ in Metabolic Disease: New Insights Into an Old MoleculeIn their review article published in the Journal of Endocrine Society in 2017, Elhassan et al. explore the potential of targeting nicotinamide adenine dinucleotide (NAD+) in metabolic diseases, offering new insights into this well-known molecule. The authors delve into the multifaceted roles of NAD+ in cellular metabolism, energy homeostasis, and redox balance, highlighting its importance in various metabolic pathways. They discuss emerging research elucidating the link between NAD+ dysregulation and metabolic disorders such as obesity, type 2 diabetes, and cardiovascular diseases. Furthermore, the review delves into the therapeutic implications of modulating NAD+ levels, including the use of NAD+ precursors and activators of NAD+-dependent enzymes like sirtuins. Elhassan and colleagues provide a comprehensive overview of the current understanding of NAD+ biology in the context of metabolic disease, offering valuable insights into potential therapeutic strategies targeting NAD+ metabolism.Full article on https://academic.oup.com/jes/article-abstract/1/7/816/3827720
Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci. 2019;26(1):34. Published 2019 May 11. doi:10.1186/s12929-019-0527-8.View Summary –Implications of altered NAD metabolism in metabolic disordersIn their 2019 publication in the Journal of Biomedical Science, Okabe et al. discuss the implications of altered nicotinamide adenine dinucleotide (NAD) metabolism in metabolic disorders. The authors provide insights into how dysregulation of NAD metabolism contributes to the pathogenesis of various metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disorders. They explore the role of NAD in cellular energy metabolism, mitochondrial function, and regulation of key metabolic pathways such as glycolysis, fatty acid oxidation, and oxidative phosphorylation. Additionally, Okabe and colleagues discuss emerging evidence linking NAD metabolism to cellular stress responses, inflammation, and insulin signaling pathways. By summarizing recent research findings, the authors highlight the potential of targeting NAD metabolism as a therapeutic approach for treating metabolic disorders. Their review provides valuable insights into the complex interplay between NAD metabolism and metabolic health, paving the way for future studies and therapeutic interventions in this field.Full article on https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0527-8
Prolla TA, Denu JM. NAD+ deficiency in age-related mitochondrial dysfunction. Cell Metab. 2014;19(2):178-180. doi:10.1016/j.cmet.2014.01.005.View Summary –NAD+ deficiency in age-related mitochondrial dysfunctionIn their 2014 article published in Cell Metabolism, Prolla and Denu address the role of nicotinamide adenine dinucleotide (NAD+) deficiency in age-related mitochondrial dysfunction. The authors highlight the critical importance of NAD+ in maintaining mitochondrial function and energy metabolism, emphasizing its roles as a coenzyme for various enzymes involved in cellular processes such as glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. They discuss how NAD+ levels decline with age, leading to impaired mitochondrial function, increased oxidative stress, and reduced energy production. Prolla and Denu also explore potential mechanisms underlying NAD+ depletion in aging, including decreased NAD+ biosynthesis, increased NAD+ consumption by enzymes such as poly(ADP-ribose) polymerases (PARPs) and sirtuins, and altered NAD+ salvage pathways. By elucidating the link between NAD+ deficiency and age-related mitochondrial dysfunction, the authors underscore the importance of NAD+ replenishment strategies as potential interventions to mitigate age-related decline in mitochondrial function and associated pathologies. Their insights contribute to our understanding of the molecular mechanisms underlying aging and hold promise for the development of novel therapeutic approaches targeting NAD+ metabolism to promote healthy aging.Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00011-4.pdf
Seo KS, Kim JH, Min KN, et al. KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts. Front Neurol. 2018;9:552. Published 2018 Jul 5. doi:10.3389/fneur.2018.00552.View Summary –KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS FibroblastsIn their 2018 study published in Frontiers in Neurology, Seo et al. investigated the potential therapeutic effects of KL1333, a novel NAD+ modulator, on energy metabolism and mitochondrial dysfunction in fibroblasts from individuals with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a mitochondrial disorder characterized by impaired mitochondrial function and energy metabolism. The authors found that treatment with KL1333 improved energy metabolism and mitochondrial function in MELAS fibroblasts, as evidenced by enhanced ATP production, improved mitochondrial membrane potential, and increased mitochondrial respiration rates. Additionally, KL1333 treatment led to a reduction in reactive oxygen species (ROS) levels and improved cellular viability in MELAS fibroblasts. These findings suggest that KL1333 may have therapeutic potential for mitigating mitochondrial dysfunction and associated symptoms in MELAS and other mitochondrial disorders. The study contributes to our understanding of NAD+ modulation as a potential strategy for targeting mitochondrial dysfunction and improving cellular energetics in mitochondrial diseases.Full article on https://www.frontiersin.org/articles/10.3389/fneur.2018.00552/full
Goody MF, Henry CA. A need for NAD+ in muscle development, homeostasis, and aging. Skelet Muscle. 2018;8(1):9. Published 2018 Mar 7. doi:10.1186/s13395-018-0154-1.View Summary –A need for NAD+ in muscle development, homeostasis, and agingIn their 2018 review published in Skeletal Muscle, Goody and Henry underscored the essential role of nicotinamide adenine dinucleotide (NAD⁺) in muscle development, homeostasis, and aging. They discussed the importance of NAD⁺ as a coenzyme involved in various cellular processes critical for muscle function, including energy metabolism, mitochondrial biogenesis, and stress response pathways. Additionally, they highlighted emerging evidence suggesting that dysregulation of NAD⁺ metabolism may contribute to age-related muscle decline and proposed NAD⁺ supplementation as a potential strategy to promote muscle health and combat aging-related muscle dysfunction.Full article on https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0154-1
Lightowlers RN, Chrzanowska-Lightowlers ZM. Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?. EMBO Mol Med. 2014;6(6):705-707. doi:10.15252/emmm.201404179.View Summary –Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?In their 2014 commentary published in EMBO Molecular Medicine, Lightowlers and Chrzanowska-Lightowlers discuss the potential therapeutic implications of increasing NAD+ levels for treating mitochondrial myopathy. Mitochondrial myopathy is a group of disorders characterized by impaired mitochondrial function, leading to muscle weakness and other symptoms. The authors propose that boosting NAD+ levels could be a promising approach for treating mitochondrial myopathy, as NAD+ plays a critical role in mitochondrial function, energy metabolism, and cellular homeostasis. They highlight emerging research suggesting that NAD+ supplementation or modulation of NAD+ metabolism could enhance mitochondrial function, improve energy production, and alleviate symptoms in mitochondrial diseases. However, they also acknowledge the need for further preclinical and clinical studies to evaluate the efficacy and safety of NAD+-based therapies for mitochondrial myopathy. Overall, the commentary provides insights into the potential of NAD+ modulation as a therapeutic strategy for mitochondrial disorders and underscores the importance of continued research in this area.Full article on https://www.embopress.org/doi/abs/10.15252/emmm.201404179
Srivastava S. Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders. ClinTransl Med. 2016;5(1):25. doi:10.1186/s40169-016-0104-7.View Summary –Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disordersIn the 2016 article published in Clinical and Translational Medicine, Srivastava explores the emerging therapeutic roles of NAD+ metabolism in mitochondrial and age-related disorders. The review discusses the importance of NAD+ in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. It highlights recent findings implicating dysregulated NAD+ metabolism in the pathogenesis of mitochondrial dysfunction and age-related diseases, such as neurodegenerative disorders, metabolic syndrome, and cardiovascular diseases. The article also discusses potential therapeutic strategies targeting NAD+ metabolism, such as NAD+ precursors supplementation, modulation of NAD+-consuming enzymes, and activation of NAD+-dependent signaling pathways. By providing an overview of the current understanding of NAD+ metabolism and its implications for health and disease, the article contributes to the growing interest in NAD+ as a potential therapeutic target for mitigating age-related and mitochondrial disorders.Full article on https://link.springer.com/article/10.1186/s40169-016-0104-7
Yang Y, Sauve AA. NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. BiochimBiophysActa. 2016;1864(12):1787-1800. doi:10.1016/j.bbapap.2016.06.014.View Summary –NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapyIn their 2016 article published in Biochimica et Biophysica Acta, Yang and Sauve comprehensively review the bioenergetics, signaling roles, and therapeutic manipulation of NAD+ metabolism. The article discusses the central role of NAD+ in cellular energy metabolism, highlighting its involvement in key biochemical pathways such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Additionally, the review explores the diverse signaling functions of NAD+, including its role as a substrate for NAD+-consuming enzymes such as sirtuins, PARPs, and CD38/CD157, which regulate various cellular processes including DNA repair, gene expression, and stress response. Furthermore, the authors discuss strategies for manipulating NAD+ metabolism for therapeutic purposes, such as NAD+ precursor supplementation, modulation of NAD+-consuming enzymes, and activation of NAD+-dependent signaling pathways. By providing a comprehensive overview of NAD+ metabolism and its potential therapeutic applications, the article contributes to our understanding of the multifaceted roles of NAD+ in cellular physiology and pathology.Full article on https://www.sciencedirect.com/science/article/pii/S1570963916301236
Liu D, Pitta M, Mattson MP. Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restriction. Ann N Y Acad Sci. 2008;1147:275-282. doi:10.1196/annals.1427.028.View Summary –Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restrictionIn their 2008 article published in the Annals of the New York Academy of Sciences, Liu, Pitta, and Mattson investigate the protective effects of preventing NAD+ depletion on neurons against excitotoxicity. The study explores the bioenergetic effects of mild mitochondrial uncoupling and caloric restriction in preserving NAD+ levels and neuronal function. Through experimental models, the authors demonstrate that interventions aimed at maintaining NAD+ levels, such as mild mitochondrial uncoupling and caloric restriction, can mitigate excitotoxic neuronal damage by preserving cellular energy homeostasis and enhancing mitochondrial function. The findings suggest that strategies targeting NAD+ metabolism may hold therapeutic potential for neuroprotection against excitotoxicity and other neurodegenerative conditions. This study underscores the importance of NAD+ preservation in neuronal health and highlights the potential of NAD+-related interventions as a strategy for neuroprotection.Full article on https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1427.028
Brennan AM, Connor JA, Shuttleworth CW. NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function. J. Cereb. Blood Flow Metab. 2006;26:1389–1406.View Summary –NAD (P) H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial functionIn their 2006 study published in the Journal of Cerebral Blood Flow and Metabolism, Brennan, Connor, and Shuttleworth investigate the dynamics of NAD(P)H fluorescence transients following synaptic activity in brain slices, with a focus on the role of mitochondrial function. Using fluorescence imaging techniques, the researchers observed changes in NAD(P)H fluorescence intensity as a proxy for mitochondrial redox state in response to synaptic stimulation. Their findings indicate that synaptic activity induces transient changes in NAD(P)H fluorescence, primarily reflecting alterations in mitochondrial function. These changes are suggestive of metabolic demand and highlight the importance of mitochondrial activity in meeting the energy needs associated with synaptic transmission. The study contributes to our understanding of the relationship between neuronal activity, mitochondrial function, and cellular metabolism in the brain, providing insights into the mechanisms underlying brain energy metabolism and neurotransmission.Full article on https://journals.sagepub.com/doi/abs/10.1038/sj.jcbfm.9600292
Yaku, K., Okabe, K., Gulshan, M. et al. Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD). Sci Rep 9, 13102 (2019). https://doi.org/10.1038/s41598-019-49547-6. View Summary –Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)In their 2006 study published in the Journal of Cerebral Blood Flow and Metabolism, Brennan, Connor, and Shuttleworth investigate the dynamics of NAD(P)H fluorescence transients following synaptic activity in brain slices, with a focus on the role of mitochondrial function. Using fluorescence imaging techniques, the researchers observed changes in NAD(P)H fluorescence intensity as a proxy for mitochondrial redox state in response to synaptic stimulation. Their findings indicate that synaptic activity induces transient changes in NAD(P)H fluorescence, primarily reflecting alterations in mitochondrial function. These changes are suggestive of metabolic demand and highlight the importance of mitochondrial activity in meeting the energy needs associated with synaptic transmission. The study contributes to our understanding of the relationship between neuronal activity, mitochondrial function, and cellular metabolism in the brain, providing insights into the mechanisms underlying brain energy metabolism and neurotransmission.Full article on https://www.nature.com/articles/s41598-019-49547-6
Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res. 2018;11:1178646918776658. Published 2018 May 21. doi:10.1177/1178646918776658.View Summary +
Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ MetabolomeDuring a 6 Hour Intravenous Infusion of NAD. Front Aging Neurosci. 2019;11:257. Published 2019 Sep 12. doi:10.3389/fnagi.2019.00257.View Summary –A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ MetabolomeDuring a 6 Hour Intravenous Infusion of NADIn their pilot study published in Frontiers in Aging Neuroscience in 2019, Grant et al. investigated changes in the human plasma and urine NAD+ metabolome during a 6-hour intravenous infusion of NAD+. The researchers aimed to understand the dynamics of NAD+ metabolism in response to exogenous NAD+ administration, which has garnered interest due to its potential therapeutic implications in age-related conditions. Through comprehensive analysis of plasma and urine samples collected during the infusion, the study provided insights into the pharmacokinetics and metabolism of NAD+ in humans. The findings contribute to our understanding of NAD+ metabolism and may inform future studies exploring the therapeutic benefits of NAD+ supplementation in aging and age-related diseases.Full article on https://www.frontiersin.org/articles/10.3389/fnagi.2019.00257/full
Lloret A, Beal MF. PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochem Res. 2019;44(10):2423-2434. doi:10.1007/s11064-019-02809-1.View Summary –PGC-1α, sirtuins and PARPs in Huntington’s disease and other neurodegenerative conditions: NAD+ to rule them allIn their review article published in Neurochemical Research in 2019, Lloret and Beal explored the roles of PGC-1α, sirtuins, and PARPs in Huntington’s disease (HD) and other neurodegenerative conditions, highlighting the pivotal role of NAD+ in regulating these pathways. The authors discuss how dysregulation of NAD+ metabolism contributes to the pathogenesis of HD and other neurodegenerative diseases, emphasizing the potential therapeutic implications of targeting NAD+ metabolism to modulate these pathways. By providing a comprehensive overview of the interplay between PGC-1α, sirtuins, PARPs, and NAD+ in neurodegeneration, the review sheds light on potential therapeutic strategies aimed at restoring NAD+ levels and mitigating disease progression.Full article on https://link.springer.com/article/10.1007/s11064-019-02809-1
Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888. Published 2007 Jan 1. doi:10.2741/2194.View Summary –NAD+ and NADH in brain functions, brain diseases and brain agingIn his comprehensive review published in Frontiers in Bioscience in 2007, Ying delves into the roles of NAD+ and NADH in brain functions, diseases, and aging. The review provides insights into the diverse functions of NAD+ and NADH in cellular metabolism, energy production, and redox reactions within the brain. Furthermore, Ying discusses how dysregulation of NAD+ and NADH levels contributes to the pathogenesis of various brain diseases and disorders, including neurodegenerative diseases and aging-related cognitive decline. By synthesizing findings from numerous studies, the review highlights the importance of NAD+ and NADH in maintaining brain health and suggests potential therapeutic strategies for targeting NAD+ metabolism to combat brain diseases and age-related decline.Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Liu D, Gharavi R, Pitta M, Gleichmann M, Mattson MP. Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons. Neuromolecular Med. 2009;11(1):28-42. doi:10.1007/s12017-009-8058-1.View Summary –Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neuronsIn their study published in Neuromolecular Medicine in 2009, Liu et al. investigate the neuroprotective effects of nicotinamide, a precursor of NAD+, against excitotoxicity and cerebral ischemia-induced neuronal damage. The researchers demonstrate that nicotinamide prevents NAD+ depletion, thereby safeguarding neurons from excitotoxicity and ischemic insults. They propose that the neuroprotective mechanism involves the preservation of NAD+ levels, which are essential for maintaining cellular energy metabolism and redox balance. Furthermore, the study suggests that excessive NAD+ consumption by SIRT1, a NAD+-dependent protein deacetylase, may compromise the viability of energetically compromised neurons. Overall, the findings highlight the potential therapeutic benefits of nicotinamide in mitigating neuronal damage associated with excitotoxicity and ischemic events, offering insights into the role of NAD+ metabolism in neuroprotection.Full article on https://link.springer.com/article/10.1007/s12017-009-8058-1
Liu J, Yang B, Zhou P, et al. Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage. Sci Rep. 2017;7(1):7321. Published 2017 Aug 4. doi:10.1038/s41598-017-07343-0.View Summary –Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stageIn their study published in Scientific Reports in 2017, Liu et al. investigate the role of nicotinamide adenine dinucleotide (NAD+) in suppressing epileptogenesis at an early stage. The researchers demonstrate that NAD+ administration exerts a suppressive effect on the development of epilepsy in experimental models. Specifically, they find that early intervention with NAD+ attenuates the progression of epileptogenesis, reducing the frequency and severity of seizures. This protective effect is associated with the modulation of neuronal excitability and synaptic transmission in the hippocampus, a brain region critical for epileptogenesis. The findings suggest that NAD+ may represent a potential therapeutic strategy for preventing the onset of epilepsy or delaying its progression, offering insights into the role of NAD+ metabolism in epileptogenesis.Full article on https://www.nature.com/articles/s41598-017-07343-0
Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci. 2010;30(8):2967-2978. doi:10.1523/JNEUROSCI.5552-09.2010.View Summary –NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal deathIn their study published in the Journal of Neuroscience in 2010, Alano et al. investigate the role of nicotinamide adenine dinucleotide (NAD+) depletion in poly(ADP-ribose) polymerase-1 (PARP-1)-mediated neuronal death. The researchers demonstrate that NAD+ depletion is both necessary and sufficient for PARP-1 activation and subsequent neuronal death. They show that the depletion of NAD+ leads to the overactivation of PARP-1, resulting in the excessive consumption of NAD+ and ATP, DNA damage, and ultimately, neuronal death. Moreover, they identify mitochondrial dysfunction as a key consequence of PARP-1 activation, further contributing to neuronal demise. These findings highlight the critical role of NAD+ depletion in PARP-1-mediated neuronal death and suggest potential therapeutic targets for neuroprotection in conditions associated with NAD+ depletion and PARP-1 activation, such as ischemic stroke and neurodegenerative diseases.Full article on https://www.jneurosci.org/content/30/8/2967?ct=ct
Hou Y, Lautrup S, Cordonnier S, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. ProcNatlAcadSci U S A. 2018;115(8):E1876-E1885. doi:10.1073/pnas.1718819115.View Summary –NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiencyIn their study published in the Proceedings of the National Academy of Sciences of the United States of America in 2018, Hou et al. investigate the effects of nicotinamide adenine dinucleotide (NAD+) supplementation on Alzheimer’s disease (AD) features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. The researchers demonstrate that NAD+ supplementation normalizes key AD features, including synaptic plasticity, learning and memory deficits, and neuroinflammation. Furthermore, NAD+ supplementation enhances DNA repair mechanisms and reduces DNA damage accumulation in the brain. These findings suggest that NAD+ supplementation holds promise as a therapeutic intervention for AD by targeting both AD pathology and DNA damage responses.Full article on https://www.pnas.org/doi/abs/10.1073/pnas.1718819115
Xing S, Hu Y, Huang X, Shen D, Chen C. Nicotinamidephosphoribosyltransferase‑related signaling pathway in early Alzheimer’s disease mouse models. Mol Med Rep. 2019;20(6):5163-5171. doi:10.3892/mmr.2019.10782.View Summary –Nicotinamidephosphoribosyltransferase‑related signaling pathway in early Alzheimer’s disease mouse modelsIn their study published in Molecular Medicine Reports in 2019, Xing et al. investigated the nicotinamide phosphoribosyltransferase (NAMPT)-related signaling pathway in early Alzheimer’s disease (AD) mouse models. The researchers focused on understanding the role of NAMPT, an enzyme involved in the synthesis of nicotinamide adenine dinucleotide (NAD+), in the pathogenesis of AD. They found that NAMPT expression levels were decreased in the hippocampus of AD mice compared to control mice. Additionally, they observed alterations in downstream signaling pathways associated with NAMPT, including the sirtuin pathway and the AMP-activated protein kinase (AMPK) pathway. These findings suggest that dysregulation of NAMPT-related signaling pathways may contribute to the early stages of AD pathology, highlighting the potential therapeutic targets for AD treatment.Full article on https://www.spandidos-publications.com/mmr/20/6/5163?mc_cid=a9ffcb1686&mc_eid=0ad572b0de
Braidy N, Grant R, Sachdev PS. Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer’s disease. CurrOpin Psychiatry. 2018;31(2):160-166. doi:10.1097/YCO.0000000000000394.View Summary –Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer’s diseaseIn their review article published in Current Opinion in Psychiatry in 2018, Braidy, Grant, and Sachdev discussed the potential therapeutic role of nicotinamide adenine dinucleotide (NAD+) and its related precursors in the treatment of Alzheimer’s disease (AD). They highlighted the importance of NAD+ in various cellular processes, including energy metabolism, DNA repair, and regulation of gene expression. The authors also reviewed preclinical and clinical studies investigating the use of NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in AD models and patients. They discussed the potential of NAD+ supplementation to mitigate AD-related pathologies, such as mitochondrial dysfunction, oxidative stress, and neuroinflammation. Additionally, they emphasized the need for further research to elucidate the efficacy and safety of NAD+ precursors as potential therapeutic agents for AD.Full article on https://www.ingentaconnect.com/content/wk/yco/2018/00000031/00000002/art00015
Demarin V, Podobnik SS, Storga-Tomic D, Kay G. Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs ExpClin Res. 2004;30(1):27-33.View Summary –Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind studyIn a randomized, double-blind study published in Drugs in Experimental and Clinical Research in 2004, Demarin et al. investigated the treatment of Alzheimer’s disease (AD) with stabilized oral nicotinamide adenine dinucleotide (NAD+). The study aimed to assess the efficacy and safety of NAD+ supplementation in AD patients. The researchers conducted a clinical trial involving AD patients who were randomly assigned to receive either stabilized oral NAD+ or placebo for a specified duration. They evaluated various clinical parameters, including cognitive function, activities of daily living, and global clinical status, to assess the effects of NAD+ supplementation on AD symptoms. The findings of this study provided insights into the potential use of NAD+ as a therapeutic intervention for AD, although further research is needed to confirm these findings and elucidate the underlying mechanisms of action.Full article on https://europepmc.org/article/med/15134388
Fang EF, Hou Y, Lautrup S, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10(1):5284. Published 2019 Nov 21. doi:10.1038/s41467-019-13172-8.View Summary –NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndromeIn a study published in Nature Communications in 2019, Fang et al. investigated the effects of NAD+ augmentation on mitophagy and accelerated aging in Werner syndrome. Werner syndrome is a genetic disorder characterized by premature aging and an increased risk of age-related diseases. The researchers found that NAD+ augmentation restored mitophagy, the process by which damaged mitochondria are removed, and limited accelerated aging in a mouse model of Werner syndrome. These findings suggest that NAD+ augmentation may have therapeutic potential for treating age-related diseases associated with mitochondrial dysfunction. Further research is needed to elucidate the underlying mechanisms and potential clinical applications of NAD+ augmentation in age-related disorders.Full article on https://www.nature.com/articles/s41467-019-13172-8
Dong, Y., Sameni, S., Digman, M.A. et al. Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer’s Disease Neurons by Imposed External Cys/CySS Redox Shifts. Sci Rep 9, 11274 (2019). https://doi.org/10.1038/s41598-019-47582-x.View Summary –Reversibility of age-related oxidized free NADH redox states in Alzheimer’s disease neurons by imposed external Cys/CySS redox shiftsIn their 2019 study published in Scientific Reports, Dong et al. investigated the reversibility of age-related oxidized free NADH redox states in Alzheimer’s disease neurons by imposed external Cys/CySS redox shifts. They found that age-related oxidized free NADH redox states in Alzheimer’s disease neurons could be reversed by imposed external Cys/CySS redox shifts. This suggests that interventions targeting redox regulation could potentially mitigate age-related alterations in cellular metabolism associated with Alzheimer’s disease. Further research is warranted to explore the therapeutic implications of these findings and their potential application in developing novel treatments for Alzheimer’s disease.Full article on https://www.nature.com/articles/s41598-019-47582-x
Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J. S., Zhang, H., D’Amico, D., Moullan, N., Potenza, F., Schmid, A. W., Rietsch, S., Counts, S. E., & Auwerx, J. (2017). Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature, 552(7684), 187–193. https://doi.org/10.1038/nature25143.View Summary +
Wu, L. E., Gomes, A. P., & Sinclair, D. A. (2014). Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer cell, 25(1), 12–19. https://doi.org/10.1016/j.ccr.2013.12.005.View Summary +
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., Hahn, W. C., Guarente, L. P., & Sinclair, D. A. (2008). The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PloS one, 3(4), e2020. https://doi.org/10.1371/journal.pone.0002020.View Summary +
Sebastián, C., Zwaans, B. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., Cosentino, C., Greenson, J. K., MacDonald, A. I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Bernstein, B. E., … Mostoslavsky, R. (2012). The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell, 151(6), 1185–1199. https://doi.org/10.1016/j.cell.2012.10.047.View Summary +
Lee MK, Cheong HS, Koh Y, Ahn KS, Yoon SS, Shin HD. Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population. Genet Test Mol Biomarkers. 2016;20:696–701.View Summary +
Dollerup O.L., Christensen B., Svart M., Schmidt M.S., Sulek K., Ringgaard S., Stødkilde-Jørgensen H., Møller N., Brenner C., Treebak J.T., Jessen N. A randomized placebo-controlled clinical trial of nicotinamideriboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am. J. Clin. Nutr. 2018;108:343–353.View Summary +
Martens C.R., Denman B.A., Mazzo M.R., Armstrong M.L., Reisdorph N., McQueen M.B., Chonchol M., Seals D.R. Chronic nicotinamideriboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat. Commun. 2018;9:1286.View Summary –Chronic nicotinamideriboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adultsIn their 2018 study published in Nature Communications, Martens et al. investigated the effects of chronic nicotinamide riboside (NR) supplementation on NAD+ levels in healthy middle-aged and older adults. The researchers conducted a randomized, double-blind, placebo-controlled trial in which participants were assigned to receive either NR supplementation or a placebo for a specified period. They monitored the participants’ NAD+ levels and assessed the tolerability of NR supplementation throughout the study. The results showed that chronic NR supplementation was well-tolerated by the participants and led to a significant increase in NAD+ levels compared to the placebo group. These findings suggest that NR supplementation may effectively elevate NAD+ levels in middle-aged and older adults, potentially providing benefits for age-related physiological decline.Full article on https://www.nature.com/articles/s41467-018-03421-7
Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018;8:622. Published 2018 Dec 12. doi:10.3389/fonc.2018.00622.View Summary –NAD Metabolism in Cancer TherapeuticsThe paper “NAD Metabolism in Cancer Therapeutics” by Yaku et al., published in Frontiers in Oncology in 2018, discusses the role of nicotinamide adenine dinucleotide (NAD) metabolism in cancer and its therapeutic implications. The authors delve into the various aspects of NAD metabolism, including its synthesis, consumption, and regulation, and how alterations in NAD levels and NAD-dependent enzymes contribute to tumorigenesis and cancer progression. Furthermore, the paper explores potential therapeutic strategies targeting NAD metabolism for cancer treatment, such as modulating NAD levels, inhibiting NAD-consuming enzymes, and enhancing NAD-dependent processes. Overall, the review provides valuable insights into the complex interplay between NAD metabolism and cancer biology, highlighting the potential of targeting NAD pathways as a promising avenue for cancer therapy.Full article on https://www.frontiersin.org/articles/10.3389/fonc.2018.00622/full
Available from https://www.biorxiv.org/content/10.1101/2020.03.21.001123v1. View Summary -The provided link directs to a preprint version of a scientific article titled “NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice” by Zhang et al., which was deposited on the bioRxiv preprint server. This study investigates the effects of nicotinamide adenine dinucleotide (NAD+) supplementation on mitochondrial function, stem cell activity, and lifespan in mice. The findings suggest that NAD+ repletion has beneficial effects on mitochondrial health, stem cell function, and longevity. However, it’s important to note that preprints have not undergone peer review and should be interpreted with caution until they are published in a peer-reviewed journal.Full article on https://www.biorxiv.org/content/10.1101/2020.03.21.001123v1
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.View Summary –Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in miceThe study titled “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice” by Sundaresan et al. examines the role of Sirt3, a member of the sirtuin family of NAD+-dependent protein deacetylases, in protecting against cardiac hypertrophy. The research demonstrates that Sirt3 plays a crucial role in mitigating the cardiac hypertrophic response by enhancing the antioxidant defense mechanisms regulated by Foxo3a. The findings suggest that Sirt3 activation could be a potential therapeutic strategy for preventing cardiac hypertrophy and related cardiovascular diseases. The article was published in The Journal of Clinical Investigation in 2009.Full article on https://www.jci.org/articles/view/39162
Hafner, A. V., Dai, J., Gomes, A. P., Xiao, C. Y., Palmeira, C. M., Rosenzweig, A., & Sinclair, D. A. (2010). Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging, 2(12), 914–923. https://doi.org/10.18632/aging.100252.View Summary –Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophyThe study titled “Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy” by Hafner et al. investigates the role of SIRT3, a member of the sirtuin family, in regulating age-related cardiac hypertrophy. The research highlights that SIRT3 modulates the mitochondrial permeability transition pore (mPTP) by deacetylating cyclophilin D (CypD) at lysine 166, thereby suppressing age-related cardiac hypertrophy. This study provides insights into the molecular mechanisms underlying cardiac aging and suggests SIRT3 activation as a potential therapeutic strategy for preventing age-related cardiac hypertrophy. The article was published in Aging in 2010.Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034180/
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.View Summary –Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in miceThe study titled “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice” by Sundaresan et al. investigates the role of Sirt3, a member of the sirtuin family, in regulating cardiac hypertrophy. The research demonstrates that Sirt3 functions to mitigate cardiac hypertrophy by enhancing the antioxidant defense mechanisms mediated by Foxo3a. By promoting Foxo3a-dependent gene expression, Sirt3 effectively suppresses the hypertrophic response in cardiac cells. This study provides valuable insights into the molecular mechanisms underlying cardiac hypertrophy and suggests Sirt3 as a potential therapeutic target for treating cardiac hypertrophy-related conditions. The article was published in The Journal of Clinical Investigation in 2009.Full article on https://www.jci.org/articles/view/39162
Nacarelli, T., Lau, L., Fukumoto, T., Zundell, J., Fatkhutdinov, N., Wu, S., Aird, K. M., Iwasaki, O., Kossenkov, A. V., Schultz, D., Noma, K. I., Baur, J. A., Schug, Z., Tang, H. Y., Speicher, D. W., David, G., & Zhang, R. (2019). NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nature cell biology, 21(3), 397–407. https://doi.org/10.1038/s41556-019-0287-4.View Summary –CD38-expressing macrophages drive age-related NAD+ declineThe study titled “NAD+ metabolism governs the proinflammatory senescence-associated secretome” by Nacarelli et al. investigates the role of NAD+ metabolism in regulating the senescence-associated secretory phenotype (SASP), which contributes to age-related inflammation and pathologies. The research demonstrates that depletion of NAD+ levels, either through genetic or pharmacological means, enhances the SASP in senescent cells. Mechanistically, NAD+ depletion leads to decreased activity of the NAD+-dependent deacetylase SIRT1, resulting in increased acetylation of the transcription factor STAT3 and subsequent upregulation of proinflammatory gene expression. Conversely, supplementation with NAD+ precursors or activation of SIRT1 attenuates the SASP. These findings highlight the critical role of NAD+ metabolism in modulating the inflammatory phenotype of senescent cells and suggest potential therapeutic strategies for mitigating age-related inflammation. The article was published in Nature Cell Biology in 2019.Full article on https://www.nature.com/articles/s42255-020-00292-5
Gong B, Pan Y, Vempati P, et al. Nicotinamideriboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging. 2013;34(6):1581-1588. doi:10.1016/j.neurobiolaging.2012.12.005.View Summary +
Matasic DS, Brenner C, London B. Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease. Am J Physiol Heart Circ Physiol. 2018;314(4):H839-H852. doi:10.1152/ajpheart.00409.2017.View Summary +
Alano CC, Tran A, Tao R, Ying W, Karliner JS, Swanson RA. Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. J Neurosci Res 85: 3378–3385, 2007. doi:10.1002/jnr.21479.View Summary +
De Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, Imai S, Seals DR. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15: 522–530, 2016. doi:10.1111/acel.12461.View Summary +
Alano CC, Tran A, Tao R, Ying W, Karliner JS, Swanson RA. Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. J Neurosci Res 85: 3378–3385, 2007. doi:10.1002/jnr.21479.View Summary +
Liu L, Wang P, Liu X, He D, Liang C, Yu Y. Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway. FundamClinPharmacol. 2014;28(2):180-189. doi:10.1111/fcp.12016.View Summary +
Ryu D, Zhang H, Ropelle ER, Sorrentino V, Mazala DA, Mouchiroud L, Marshall PL, Campbell MD, Ali AS, Knowels GM, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. SciTransl Med. 2016;8:361ra139.View Summary +
Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep. 2015;13:533–545.View Summary +
Chan PK, Torres R, Yandim C, Law PP, Khadayate S, Mauri M, Grosan C, Chapman-Rothe N, Giunti P, Pook M, et al. Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich’s ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum Mol Genet. 2013;22:2662–2675.View Summary +
Martin AS, Abraham DM, Hershberger KA, Bhatt DP, Mao L, Cui H, Liu J, Liu X, Muehlbauer MJ, Grimsrud PA, et al. Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model. JCI Insight. 2017;2.View Summary +
Katsyuba, E., Romani, M., Hofer, D. et al. NAD+ homeostasis in health and disease. Nat Metab 2, 9–31 (2020). https://doi.org/10.1038/s42255-019-0161-5. View Summary +
Walker MA, Tian R. Raising NAD in Heart Failure: Time to Translate?. Circulation. 2018;137(21):2274-2277. doi:10.1161/CIRCULATIONAHA.117.032626.View Summary +
Airhart SE, Shireman LM, Risler LJ, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamideriboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017;12(12):e0186459. Published 2017 Dec 6. doi:10.1371/journal.pone.0186459.View Summary +
Lee CF, Caudal A, Abell L, NaganaGowda GA, Tian R. Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease. Sci Rep. 2019;9(1):3073. Published 2019 Feb 28. doi:10.1038/s41598-019-39419-4.View Summary +
Zhou, B., Wang, D. D., Qiu, Y., Airhart, S., Liu, Y., Stempien-Otero, A., O’Brien, K. D., & Tian, R. (2020). Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. The Journal of clinical investigation, 130(11), 6054–6063. https://doi.org/10.1172/JCI138538.View Summary +
Hsu, C. P., Oka, S., Shao, D., Hariharan, N., & Sadoshima, J. (2009). Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circulation research, 105(5), 481–491. https://doi.org/10.1161/CIRCRESAHA.109.203703.View Summary +
Karamanlidis, G., Lee, C. F., Garcia-Menendez, L., Kolwicz, S. C., Jr, Suthammarak, W., Gong, G., Sedensky, M. M., Morgan, P. G., Wang, W., & Tian, R. (2013). Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell metabolism, 18(2), 239–250. https://doi.org/10.1016/j.cmet.2013.07.002.View Summary +
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